Since then, the label has been revised many times. Adverse side effects have been reported, in some cases serious and systemic.
The exact mechanism of action in which imiquimod and its analogs activate the immune system is not yet known. Nevertheless, it is known that imiquimod activates immune cells by ligating the toll-like receptor 7 (TLR7), commonly involved in pathogen recognition, on the cell surface. Cells activated by imiquimod via TLR-7 secrete cytokines (primarily interferon-α (IFN-α), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)). There is evidence that imiquimod, when applied to skin, can lead to the activation of Langerhans cells, which subsequently migrates to local lymph nodes to activate the adaptive immune system. Other cell types activated by imiquimod include natural killer cells, macrophages and B-lymphocytes.
New research has shown that imiquimod's anti-proliferative effect is totally independent of immune system activation or function. Imiquimod exerts its effect by increasing levels of the opioid growth factor receptor (OGFr). Blocking OGFr function with siRNA technology resulted in loss of any antiproliferative effect of imiquimod.